From studies employing immunosuppressed infected mice as recipients of immune lymphoid cells or serum, infections produced by Sindbis virus (SV), an alphavirus, induce and appear to be eliminated by antiviral antibodies; cell-mediated effector functions are either unimportant or not expressed. In contrast, virus elimination following infections with vaccinia (VAC) virus, a poxvirus, is associated with the induction of virus-specific cytotoxic T lymphocytes (CTL); antibodies seem to play a minor role. Undoubtedly, virus- and host-associated factors determine whether the class of immune response to a given infection will be predominantly humoral or cellular as well as which class will be effective in eliminating infection. From existing evidence, we believe that a major factor is the manner in which virus is first presented to the immune system and that procedures which physically alter the association between virus and antigen-presenting cells may subvert one class of response and favor the other. Recently, we have found that mice with established SV infections can be protected against lethal CNS disease by passively administered SV-specific monoclonal antibodies specific for either of the two viral envelope glycoproteins. Protection by a given antibody seems not to correlate with its virus-neutralizing activity, in vitro. The objectives of this project are: (1) to study and define the conditions in which either CTL or antibodies are induced preferentially in mice to VAC virus; (2) to establish and compare, in vitro, the requirements for secondary triggering of VAC-specific T cells induced during immune responses of each class; (3) to determine the mechanism(s) by which SV infections of the murine CNS are prevented or aborted by anti-SV monoclonal antibodies of different specificities.